A novel nonmyeloablative conditioning regimen was investigated in 44 patients with hematologic malignancies. The median patient age was 41 years. Many of the patients had high-risk features, including 19 patients with...
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A novel nonmyeloablative conditioning regimen was investigated in 44 patients with hematologic malignancies. The median patient age was 41 years. Many of the patients had high-risk features, including 19 patients with a previous failed transplant. Recipient conditioning consisted of CAMPATH-1H, 20 mg/day on days -8 to -4;fludarabine, 30 mg/m(2) on days -7 to -3;and melphalan, 140 mg/m(2) on day -2. Thirty-six recipients received unmanipulated granculocyte colony-stimulating factor-mobilized peripheral blood stem cells from HLA-identical siblings, and 8 received unmanipulated marrow from matched unrelated donors. GVHD prophylaxis was with cyclosporine A alone for 38 patients and cyclosporine A plus methotrexate for 6 sibling recipients. Forty-two of the 43 evaluable patients had sustained engraftment. Results of chimerism analysis using microsatellite polymerase chain reaction indicate that 18 of 31 patients studied were full-donor chimeras while the other patients were mixed chimeras in one or more lineages. At a median follow-up of 9 months (range 3 to 29 months), 33 patients remain alive in complete remission or with no evidence of disease progression. Seven patients relapsed or progressed post-transplantation, and 4 of them subsequently died. Four patients died of regimen-related complications. There were no cases of grades III-IV acute GVHD. Only 2 patients developed grade II acute GVHD, and only 1 had chronic GVHD. The estimated probability of non-relapse mortality was 11%. Although longer follow-up is needed to establish the longterm remission rates, this study demonstrates that this nonmyeloablative preparative regimen is associated with durable engraftment, minimal toxicity, and low incidence of GVHD. (Blood. 2000;96:2419-2425) (C) 2000 by The American Society of Hematology.
A new bone marrow transplantation (BMT) method for treating severe autoimmune diseases in chimeric resistant MRL/lpr mice is presented. The method consists of fractionated irradiation (5.5 Gy x 2), followed by portal ...
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A new bone marrow transplantation (BMT) method for treating severe autoimmune diseases in chimeric resistant MRL/lpr mice is presented. The method consists of fractionated irradiation (5.5 Gy x 2), followed by portal venous (PV) injection of whole bone marrow cells (BMCs) from allogeneic normal C57BL/6 (B6) mice and intravenous (IV) injection of whole B6 BMCs 5 days after the PV injection (abbreviated as 5.5 Gy x 2 + PY + IV). AII recipients survived more than 1 year after this treatment (more than 64 weeks after birth), Abnormal T cells (Thy1.2(+)/B220(+)/CD3(+)/CD4(-)/CD8(-)) present in MRL/lpr mice before the treatment disappear, and hematolymphoid cells are reconstituted with donor-derived cells, The treated mice are free from autoimmune diseases, Levels of autoantibodies (IgG/IgM anti-ssDNA antibodies and IgG/IgM rheumatoid factors) decrease to normal levels. Successful cooperation is achieved among T cells, B cells, and antigen-presenting cells (APCs) of the treated MRL/lpr mice when evaluated by in vitro anti-SRBC responses. Newly developed T cells are tolerant to both donor (B6)-type and host (MRL/lpr)-type major histocompatibility complex (MHC) determinants. These findings clearly indicate that severe autoimmune diseases in MRL/lpr mice are completely ameliorated by the treatment without recourse to immunosuppressants, and that the treated MRL/ lpr mice show normal immune functions, strongly suggesting that this strategy would be applicable to humans. (C) 2000 by The American Society of Hematology.
Loss of self-tolerance is the basis for autoimmune disease. Autologous as well as allogeneic stem cell transplantation is increasingly being considered and used for therapy of autoimmune disease. Non-myeloablative con...
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Loss of self-tolerance is the basis for autoimmune disease. Autologous as well as allogeneic stem cell transplantation is increasingly being considered and used for therapy of autoimmune disease. Non-myeloablative conditioning has been shown in the context of malignant diseases to be feasible. Cord blood transplantation has been associated with significantly less graft-versus-host disease (GVHD) than other forms of allotransplantation. Ex-vivo expansion of this limited resource is increasingly becoming feasible. It is being hypothesized that ex-vivo expanded cord blood progenitor cell transplantation using a non-myeloablative conditioning regimen would be curative in autoimmune diseases. (C) 2000 Harcourt Publishers Ltd.
Describes the clinical features in a young man with subcutaneous panniculitic T cell lymphoma (SPTCL) originating on the right cheek, which transformed into leukemia at the time of the first relapse. Treatment given; ...
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Describes the clinical features in a young man with subcutaneous panniculitic T cell lymphoma (SPTCL) originating on the right cheek, which transformed into leukemia at the time of the first relapse. Treatment given; Findings from physical and blood examinations; Conclusion concerning the therapy for patients with SPTCL.
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